Tpo Tm41

Kimura and coworkers (38) have reported that a small organic molecule, benzodi-azepinone TM41, competes with TPO for binding to the receptor's extracellular region. A library of benzodiazepinones was synthesized and screened (using HTS automation) against the soluble form of human c-Mpl containing the ECD of c-Mpl and the human immunoglobulin Fc region (MPL-IgG). Several compounds were identified as dose-dependent inhibitors of TPO binding to MPL-IgG, but only TM41 was active in a cell-proliferation assay using UT-7/TPO cells (Fig. 3). TM41 also was shown to activate STAT5 in a human TPOR-dependent cell line and to be specific for c-Mpl, indicating that it does not activate other cytokine receptors.